GeneBe

SEPSECS

Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase

Basic information

Region (hg38): 4:25120014-25160550

Links

ENSG00000109618 ∙ NCBI:51091 ∙ OMIM:613009 ∙ HGNC:30605 ∙ Uniprot:Q9HD40 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • pontocerebellar hypoplasia type 2D (Definitive), mode of inheritance: AR
  • pontocerebellar hypoplasia type 2D (Moderate), mode of inheritance: AR
  • pontocerebellar hypoplasia type 2D (Strong), mode of inheritance: AR
  • pontocerebellar hypoplasia type 2D (Strong), mode of inheritance: AR
  • pontocerebellar hypoplasia type 2 (Supportive), mode of inheritance: AR
  • progressive cerebello-cerebral atrophy (Supportive), mode of inheritance: AR
  • pontocerebellar hypoplasia type 2D (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Pontocerebellar hypoplasia, type 2DARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic12920088; 20920667; 25044680

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEPSECS gene.

  • not_provided (458 variants)
  • Pontocerebellar_hypoplasia_type_2D (123 variants)
  • Inborn_genetic_diseases (57 variants)
  • not_specified (13 variants)
  • Pontoneocerebellar_hypoplasia (6 variants)
  • SEPSECS-related_disorder (6 variants)
  • Spinal_rigidity (1 variants)
  • Kyphosis (1 variants)
  • Progressive_limb_weakness (1 variants)
  • Elliptical_nystagmus (1 variants)
  • Severe_global_developmental_delay (1 variants)
  • Cerebellar_ataxia (1 variants)
  • Spastic_diplegia (1 variants)
  • Congenital_cerebellar_hypoplasia (1 variants)
  • Neurodegeneration (1 variants)
  • Cerebral_hypoplasia (1 variants)
  • Spastic_ataxia (1 variants)
  • Seizure (1 variants)
  • Neurodevelopmental_abnormality (1 variants)
  • Arthrogryposis_multiplex_congenita (1 variants)
  • Dysarthria (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEPSECS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016955.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
5
clinvar
176
clinvar
 182
missense
1
clinvar
8
clinvar
118
clinvar
3
clinvar
1
clinvar
 131
nonsense
14
clinvar
11
clinvar
2
clinvar
 27
start loss
1
1
 2
frameshift
31
clinvar
17
clinvar
 48
splice donor/acceptor (+/-2bp)
19
clinvar
 19
Total 47 57 125 179 1

Highest pathogenic variant AF is 0.0000818115

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SEPSECSprotein_codingprotein_codingENST00000382103 1140578
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.61e-80.84612558301651257480.000656
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.02142692700.9960.00001283260
Missense in Polyphen94105.420.891711293
Synonymous2.106995.00.7260.00000455972
Loss of Function1.601624.60.6510.00000138295

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0005070.000507
Ashkenazi Jewish0.0001990.000198
East Asian0.00005440.0000544
Finnish0.005370.00537
European (Non-Finnish)0.0002290.000229
Middle Eastern0.00005440.0000544
South Asian0.0001640.000163
Other0.0003260.000326

dbNSFP

Source: dbNSFP

Function
FUNCTION: Converts O-phosphoseryl-tRNA(Sec) to selenocysteinyl- tRNA(Sec) required for selenoprotein biosynthesis. {ECO:0000269|PubMed:17142313}.;
Pathway
Selenocompound metabolism - Homo sapiens (human);Aminoacyl-tRNA biosynthesis - Homo sapiens (human);Selenium Metabolism and Selenoproteins;Selenocysteine synthesis;Metabolism of amino acids and derivatives;selenocysteine biosynthesis;Metabolism;Selenoamino acid metabolism (Consensus)

Recessive Scores

pRec
0.156

Intolerance Scores

loftool
0.412
rvis_EVS
0
rvis_percentile_EVS
53.73

Haploinsufficiency Scores

pHI
0.223
hipred
N
hipred_score
0.353
ghis
0.579

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
N
gene_indispensability_score
0.209

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Sepsecs
Phenotype

Gene ontology

Biological process
selenocysteine incorporation;selenocysteine metabolic process;selenocysteinyl-tRNA(Sec) biosynthetic process
Cellular component
nucleus;cytoplasm;cytosol
Molecular function
tRNA binding;protein binding;phosphoseryl-selenocysteinyl-tRNA selenium transferase activity